Speakers at ICG-13

Speakers at ICG-13

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Biography

Born on October 16th 1978 in El Paso, Texas, USA (US and German citizenship)

 

Number of co-authored manuscripts: 381

 

Cumulative impact factor: 4411

 

h-index: 75 (according to Scopus)

 

Prof. Franke received his PhD from Kiel University in 2006 (summa cum laude, with exception). Two years later he became Assistant professor, being 29 years of age. In 2011, he received an endowment associate professorship, which he took on until 2016. In 2016, he became a full professor and director of the institute. Prof. Franke received the Thannhauser prize from the DGVS in 2017 and in the same year he was also named “Schleswig-Holstein Excellence Professor” by the University.

 

The main scientific interests of Prof. Franke are the development and establishment of novel high-throughput technologies, the inherent bioinformatic integration and application of both to identify genetic and epigenetic causes of chronic inflammatory diseases such as Crohn’s disease, ulcerative colitis, psoriasis, primary sclerosing cholangitis, and atopic eczema. Having worked on genome-wide association studies for the last years, his research agenda currently focuses on clinical data management, whole-genome and whole-exome resequencing, microbiome analyses and immunogenetics studies. One of his prime interests is currently the search for an antigenic peptide in ulcerative colitis, for which he employs, for example, HLA fine mapping and TCR profiling.

 

The institute (IKMB) of Prof. Franke comprises over 140 employees and hosts the largest academic next-generation sequencing (NGS) facility in Germany. The IKMB is embedded into the University Hospital Schleswig-Holstein (UKSH), which is Germany’s second largest University Hospital.


Abstract

Complex immue-mediated diseases - from GWAS to host-microbiome association studies

Andre Franke 1

1 Institute of Clinical Molecular Biology (IKMB), Christian-Albrechts-University of Kiel, Kiel, Germany

Genome-wide association (GWAS) have significantly contributed to our understanding of the etiology of chronic and complex immune-mediated diseases (CID). Inflammatory bowel diseases (IBD) with its main sub phenotypes Crohn’s disease and ulcerative colitis, are prototypic CIDs that affect about 2-3 persons out of a 1000 in Western countries. IBD shares part of its genetic and immunological background with diseases like psoriasis, ankylosing spondylitis, and primary sclerosis cholangitis). To this end, over 250 genetic susceptibility loci were identified in the past 10 years through GWAS and candidate-gene association studies. Complex immunogenetics efforts are currently being undertaken to solve CID. Still, the exact cause of most CID has not been identified and components of the gut microbiome are also likely disease-causing environmental factors for CID. In particular the complex interplay between our own immune system and the microbiome needs to be investigated in detail as both a dysbiosised microbiome as well as an inappropriate immune response contribute to CID.

Here, I will present our ongoing efforts in host-microbiome association analyses and allude to the methodological challenges1 of these kind of analyses. Previously, we performed a genome-wide association study (GWAS) of the gut microbiota using two cohorts from northern Germany totaling 1,812 individuals2. Comprehensively controlling for diet and non-genetic parameters, we identified genome-wide significant associations for overall microbial variation and individual taxa at multiple genetic loci, including the VDR gene (encoding vitamin D receptor). We observed significant shifts in the microbiota of Vdr-/- mice relative to control mice and correlations between the microbiota and serum measurements of selected bile and fatty acids in humans, including known ligands and downstream metabolites of VDR. Genome-wide significant (P < 5 × 10E-8) associations at multiple additional loci identify other important points of host-microbe intersection, notably several disease susceptibility genes and sterol metabolism pathway components. Non-genetic and genetic factors each account for approximately 10% of the variation in gut microbiota in this study, whereby individual effects were relatively small.

1   Rühlemann MC, Degenhardt F, Thingholm LB, Wang J, Skiecevičienė J, Rausch P, Hov JR, Lieb W, Karlsen TH, Laudes M, Baines JF, Heinsen FA, Franke A. Application of the distance-based F test in an mGWAS investigating β diversity of intestinal microbiota identifies variants in SLC9A8 (NHE8) and 3 other loci. Gut Microbes. 2018 Jan 2;9(1):68-75. doi: 10.1080/19490976.2017.1356979.

2   Wang J, Thingholm LB, Skiecevičienė J, Rausch P, Kummen M, Hov JR, Degenhardt F, Heinsen FA, Rühlemann MC, Szymczak S, Holm K, Esko T, Sun J, Pricop-Jeckstadt M, Al-Dury S, Bohov P, Bethune J, Sommer F, Ellinghaus D, Berge RK, Hübenthal M, Koch M, Schwarz K, Rimbach G, Hübbe P, Pan WH, Sheibani-Tezerji R, Häsler R, Rosenstiel P, D'Amato M, Cloppenborg-Schmidt K, Künzel S, Laudes M, Marschall HU, Lieb W, Nöthlings U, Karlsen TH, Baines JF, Franke A. Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota. Nat Genet. 2016 Nov;48(11):1396-1406. doi: 10.1038/ng.3695.

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